Disease relevance of RPE65

• CONCLUSIONS: The informative SNPs provide evidence allowing indirect exclusion of mutations in the RPE65 gene as causing retinal degeneration in 25 of the 26 dog breeds investigated with presumed autosomal recessively transmitted gPRA [1].
• METHODS: Normal RPE65 dog cDNA was subcloned into an rAAV vector under control of a cytomegalovirus promoter, and an AAV.GFP control vector was also produced with the titers 2 x 10(12) particles/mL and 2 x 10(10) transducing U/mL, respectively [2].
• Uveitis developed in 75% of the transgene-treated eyes, a complication possibly due to an immunopathogenic response to the RPE65 molecule [2].
• Lentiviral gene transfer of RPE65 rescues survival and function of cones in a mouse model of Leber congenital amaurosis [3].

High impact information on RPE65

• Our safety studies of subretinal AAV-2/2.RPE65 in RPE65-mutant dogs showed evidence of modest photoreceptor loss in the injection region in some animals at higher vector doses [4].
• Eye movement recordings as an effectiveness indicator of gene therapy in RPE65-deficient canines: implications for the ocular motor system [5].
• Immunocytochemistry showed expression of RPE65 in the retinal pigment epithelium (RPE) of AAV.RPE65-treated eyes [2].
• In a second group of 28 dogs [16 normals, 10 RPE65 mutants, and 2 with progressive rod cone degeneration (prcd)], the 25-gauge needle of the RetinaJect was used to penetrate the conjunctiva and the sclera [6].
• The proof of feasibility of gene therapy for RPE65 deficiency has already been established in a dog model of Leber congenital amaurosis, but rescue of the cone function, although crucial for human high-acuity vision, has never been strictly proven [3].

Anatomical context of RPE65

• By gene replacement, rAAV-based photoreceptor rescue has been achieved in the rds-/- mouse and has restored vision in dogs carrying a RPE65 gene mutation [7].

Associations of RPE65 with chemical compounds

• BACKGROUND: RPE65 is specifically expressed in the retinal pigment epithelium and is essential for the recycling of 11-cis-retinal, the chromophore of rod and cone opsins [3].

Analytical, diagnostic and therapeutic context of RPE65

• Functional and structural recovery of the retina after gene therapy in the RPE65 null mutation dog [2].
• Two RPE65(-/-) dogs were killed at 3 and 6 months after treatment for morphologic examination of the retinas [2].
• LCA caused by RPE65 mutations has been studied in animal models and vision has been restored by subretinal delivery of AAV-RPE65 vector [4].

References